De novo assembly of the cattle reference genome with single-molecule sequencing.

BackgroundMajor advances in selection progress for cattle have been made following the introduction of genomic tools over the past 10-12 years. These tools depend upon the Bos taurus reference genome (UMD3.1.1), which was created using now-outdated technologies and is hindered by a variety of deficiencies and inaccuracies.ResultsWe present the new reference genome for cattle, ARS-UCD1.2, based on the same animal as the original to facilitate transfer and interpretation of results obtained from the earlier version, but applying a combination of modern technologies in a de novo assembly to increase continuity, accuracy, and completeness. The assembly includes 2.7 Gb and is >250× more continuous than the original assembly, with contig N50 >25 Mb and L50 of 32. We also greatly expanded supporting RNA-based data for annotation that identifies 30,396 total genes (21,039 protein coding). The new reference assembly is accessible in annotated form for public use.ConclusionsWe demonstrate that improved continuity of assembled sequence warrants the adoption of ARS-UCD1.2 as the new cattle reference genome and that increased assembly accuracy will benefit future research on this species

Using Model Test Data to Assess VIV Factor of Safety for SCR and TTR in GOM

This paper presents results obtained as part of the DeepStar Phase 10 program on VIV Factors of Safety. The objective was to develop a general methodology to calibrate Factors of Safety for VIV-induced fatigue and to apply it to partially straked risers. This was achieved using reliability methods, accepted industry VIV prediction software and state-of-the-art model test experiments. Most oil companies use a Factor of Safety of 20 when predicting VIV damage using VIV software tools. There are numerous software tools currently in use in industry to predict VIV damage to straked risers and each of them will have different accuracy, and therefore an intrinsic level of conservatism. Understanding the level of conservatism in different VIV prediction software is therefore critical to determining what Factor of Safety to use. This study benchmarks the latest generation of industry accepted VIV design tools at the time of the study (2011): SHEAR7v4.6, VIVAv6.5 and VIVANAv3.7.24 against high quality VIV data from three separate straked riser experiments. A bias distribution (predicted to measured VIV damage results) is obtained for each software tool as a function of the strake coverage. A novel reliability framework approach is then developed to incorporate all uncertainties associated with VIV fatigue prediction into a limit state function, including variability in met-ocean conditions and variability in the fatigue resistance of the material characterized by a design S-N curve. The limit state function is analyzed using First Order Reliability Methods to develop Factors of Safety for target probabilities of failure. The general method is then applied on two case studies involving an SCR and TTR in Gulf of Mexico loop currents, but it can be easily extended to different locations and riser configurations. The resulting FoS range from about 1 to 15 for most software, and are lower than industry standards for VIV prediction. The FoS do not vary markedly for different riser configurations, indicating the possibility of reducing excess conservatism when predicting VIV damage on straked risers.DeepStar (Consortium)SHEAR7 JI

Transcriptomic classification of genetically engineered mouse models of breast cancer identifies human subtype counterparts

Background: Human breast cancer is a heterogeneous disease consisting of multiple molecular subtypes. Genetically engineered mouse models are a useful resource for studying mammary cancers in vivo under genetically controlled and immune competent conditions. Identifying murine models with conserved human tumor features will facilitate etiology determinations, highlight the effects of mutations on pathway activation, and should improve preclinical drug testing. Results: Transcriptomic profiles of 27 murine models of mammary carcinoma and normal mammary tissue were determined using gene expression microarrays. Hierarchical clustering analysis identified 17 distinct murine subtypes. Cross-species analyses using three independent human breast cancer datasets identified eight murine classes that resemble specific human breast cancer subtypes. Multiple models were associated with human basal-like tumors including TgC3(1)-Tag, TgWAP-Myc and Trp53-/-. Interestingly, the TgWAPCre-Etv6 model mimicked the HER2-enriched subtype, a group of human tumors without a murine counterpart in previous comparative studies. Gene signature analysis identified hundreds of commonly expressed pathway signatures between linked mouse and human subtypes, highlighting potentially common genetic drivers of tumorigenesis. Conclusions: This study of murine models of breast carcinoma encompasses the largest comprehensive genomic dataset to date to identify human-to-mouse disease subtype counterparts. Our approach illustrates the value of comparisons between species to identify murine models that faithfully mimic the human condition and indicates that multiple genetically engineered mouse models are needed to represent the diversity of human breast cancers. The reported trans-species associations should guide model selection during preclinical study design to ensure appropriate representatives of human disease subtypes are used

Upsilon (1S+2S+3S) production in d+Au and p+p collisions at sqrt(s_NN)=200 GeV and cold-nuclear matter effects

The three Upsilon states, Upsilon(1S+2S+3S), are measured in d+Au and p+p collisions at sqrt(s_NN)=200 GeV and rapidities 1.2<|y|<2.2 by the PHENIX experiment at the Relativistic Heavy-Ion Collider. Cross sections for the inclusive Upsilon(1S+2S+3S) production are obtained. The inclusive yields per binary collision for d+Au collisions relative to those in p+p collisions (R_dAu) are found to be 0.62 +/- 0.26 (stat) +/- 0.13 (syst) in the gold-going direction and 0.91 +/- 0.33 (stat) +/- 0.16 (syst) in the deuteron-going direction. The measured results are compared to a nuclear-shadowing model, EPS09 [JHEP 04, 065 (2009)], combined with a final-state breakup cross section, sigma_br, and compared to lower energy p+A results. We also compare the results to the PHENIX J/psi results [Phys. Rev. Lett. 107, 142301 (2011)]. The rapidity dependence of the observed Upsilon suppression is consistent with lower energy p+A measurements.Comment: 495 authors, 11 pages, 9 figures, 5 tables. Submitted to Phys. Rev. C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Adipocyte-specific protein tyrosine phosphatase 1B deletion increases lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasis

Peer reviewedPublisher PD

Military maladaptation : counterinsurgency and the politics of failure

Tactical learning is critical to battlefield success, especially in a counterinsurgency. This article tests the existing model of military adaption against a ‘most-likely’ case: the British Army’s counterinsurgency in the Southern Cameroons (1960–61). Despite meeting all preconditions thought to enable adaptation – decentralization, leadership turnover, supportive leadership, poor organizational memory, feedback loops, and a clear threat – the British still failed to adapt. Archival evidence suggests politicians subverted bottom-up adaptation, because winning came at too high a price in terms of Britain’s broader strategic imperatives. Our finding identifies an important gap in the extant adaptation literature: it ignores politics.PostprintPeer reviewe

Measurements of elliptic and triangular flow in high-multiplicity 3^{3}He++Au collisions at sNN=200\sqrt{s_{_{NN}}}=200 GeV

We present the first measurement of elliptic ($v_2$) and triangular ($v_3$) flow in high-multiplicity $^{3}$He$+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV. Two-particle correlations, where the particles have a large separation in pseudorapidity, are compared in $^{3}$He$+$Au and in $p$$+$$p$ collisions and indicate that collective effects dominate the second and third Fourier components for the correlations observed in the $^{3}$He$+$Au system. The collective behavior is quantified in terms of elliptic $v_2$ and triangular $v_3$ anisotropy coefficients measured with respect to their corresponding event planes. The $v_2$ values are comparable to those previously measured in $d$$+$Au collisions at the same nucleon-nucleon center-of-mass energy. Comparison with various theoretical predictions are made, including to models where the hot spots created by the impact of the three $^{3}$He nucleons on the Au nucleus expand hydrodynamically to generate the triangular flow. The agreement of these models with data may indicate the formation of low-viscosity quark-gluon plasma even in these small collision systems.Comment: 630 authors, 9 pages, 4 figures, 2 tables. v2 is the version accepted for publication by Physical Review Letters. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

The effect of different dosing regimens of motesanib on the gallbladder: a randomized phase 1b study in patients with advanced solid tumors

Extent: 11 p.BACKGROUND: Gallbladder toxicity, including cholecystitis, has been reported with motesanib, an orally administered small-molecule antagonist of VEGFRs 1, 2 and 3; PDGFR; and Kit. We assessed effects of motesanib on gallbladder size and function. METHODS: Patients with advanced metastatic solid tumors ineligible for or progressing on standard-of-care therapies with no history of cholecystitis or biliary disease were randomized 2:1:1 to receive motesanib 125 mg once daily (Arm A); 75 mg twice daily (BID), 14-days-on/7-days-off (Arm B); or 75 mg BID, 5-days-on/2-days-off (Arm C). Primary endpoints were mean change from baseline in gallbladder size (volume by ultrasound; independent review) and function (ejection fraction by CCK-HIDA; investigator assessment). RESULTS: Forty-nine patients received ≥1 dose of motesanib (Arms A/B/C, n = 25/12/12). Across all patients, gallbladder volume increased by a mean 22.2 cc (from 38.6 cc at baseline) and ejection fraction decreased by a mean 19.2% (from 61.3% at baseline) during treatment. Changes were similar across arms and appeared reversible after treatment discontinuation. Three patients had cholecystitis (grades 1, 2, 3, n = 1 each) that resolved after treatment discontinuation, one patient developed grade 3 acute cholecystitis requiring cholecystectomy, and two patients had other notable grade 1 gallbladder disorders (gallbladder wall thickening, gallbladder dysfunction) (all in Arm A). Two patients developed de novo gallstones during treatment. Twelve patients had right upper quadrant pain (Arms A/B/C, n = 8/1/3). The incidence of biliary “sludge” in Arms A/B/C was 39%/36%/27%. CONCLUSION: Motesanib treatment was associated with increased gallbladder volume, decreased ejection fraction, biliary sludge, gallstone formation, and infrequent cholecystitis. Trial registration: ClinicalTrials.gov NCT00448786Lee S. Rosen, Lara Lipton, Timothy J. Price, Neil D. Belman, Ralph V. Boccia, Herbert I. Hurwitz, Joe J. Stephenson Jr., Lori J. Wirth, Sheryl McCoy, Yong-jiang Hei, Cheng-Pang Hsu and Niall C. Tebbut

Measurement of long-range angular correlation and quadrupole anisotropy of pions and (anti)protons in central dd++Au collisions at sNN\sqrt{s_{_{NN}}}=200 GeV

We present azimuthal angular correlations between charged hadrons and energy deposited in calorimeter towers in central $d$$+$Au and minimum bias $p$$+$$p$ collisions at $\sqrt{s_{_{NN}}}=200$ GeV. The charged hadron is measured at midrapidity $|\eta|<0.35$, and the energy is measured at large rapidity ($-3.7<\eta<-3.1$, Au-going direction). An enhanced near-side angular correlation across $|\Delta\eta| >$ 2.75 is observed in $d$$+$Au collisions. Using the event plane method applied to the Au-going energy distribution, we extract the anisotropy strength $v_2$ for inclusive charged hadrons at midrapidity up to $p_T=4.5$ GeV/$c$. We also present the measurement of $v_2$ for identified $\pi^{\pm}$ and (anti)protons in central $d$$+$Au collisions, and observe a mass-ordering pattern similar to that seen in heavy ion collisions. These results are compared with viscous hydrodynamic calculations and measurements from $p$$+$Pb at $\sqrt{s_{_{NN}}}=5.02$ TeV. The magnitude of the mass-ordering in $d$$+$Au is found to be smaller than that in $p$$+$Pb collisions, which may indicate smaller radial flow in lower energy $d$$+$Au collisions.Comment: 424 authors, 8 pages, and 4 figures. v2 is version accepted for publication in Phys. Rev. Lett. Published version will be at http://www.phenix.bnl.gov/phenix/WWW/info/pp1/161/ Plain text data tables will be at http://www.phenix.bnl.gov/papers.htm

Cold-nuclear-matter effects on heavy-quark production at forward and backward rapidity in d+Au collisions at sqrt(s_NN)=200 GeV

The PHENIX experiment has measured open heavy-flavor production via semileptonic decay muons over the transverse momentum range 1 < pT < 6 GeV/c at forward and backward rapidity (1.4 < |y| < 2.0) in d+Au and p+p collisions at ?sNN = 200 GeV. In central d+Au collisions an enhancement (suppression) of heavy-flavor muon production is observed at backward (forward) rapidity relative to the yield in p+p collisions scaled by the number of binary collisions. Modification of the gluon density distribution in the Au nucleus contributes in terms of anti-shadowing enhancement and shadowing suppression; however, the enhancement seen at backward rapidity exceeds expectations from this effect alone. These results, implying an important role for additional cold nuclear matter effects, serves as a key baseline for heavy-quark measurements in A+A collisions and in constraining the magnitude of charmonia breakup effects at the Relativistic Heavy Ion Collider and the Large Hadron Collider.Comment: 424 authors, 69 insitutions, 8 pages, 4 figures. Submitted to Physical Review Letters. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm